PATIENT MANAGEMENT PROBLEM

CONTINUUM: Lifelong Learning in Neurology December 2008; Volume 14(6) Acute Ischemic Stroke; pp 158-163
Gupta, Rishi; Levine, Joshua M. Relationship Disclosure: Dr Gupta has received personal compensation for activities with Concentric Medical, Inc. Dr Levine has nothing to disclose. Unlabeled Use of Products/Investigational Use Disclosure: Drs Gupta and Levine have nothing to disclose.
The following patient management problem was chosen to reinforce the subject matter presented in this issue. It emphasizes decisions facing the practicing physician. At each decision point determine how you, as the neurologist, would respond. Then answer the questions provided. The weight or "value" indicates the relative strength or weakness of the response as determined by the faculty. Use these values, as well as the critical comments, to assess your own understanding and handling of the problem. A review of all responses, not merely the ones you select, is recommended.

Educational Objective
Neurologists are often consulted in the treatment of acute ischemic stroke. This patient management problem helps to reinforce the key issues neurologists face in the emergency department at the time of an acute ischemic stroke and helps to address some of the practical patient management issues that may occur.

Case History
A 75-year-old man with a history of hypertension and atrial fibrillation presents to the emergency department 90 minutes from last being seen normal with a left gaze deviation, global aphasia, and rightsided hemiplegia. At the time of arrival to the emergency department, his NIH Stroke Scale (NIHSS) score is 24. Past medical/social history. The patient had been scheduled for a colonoscopy to be performed in 2 days and had held the last dose of his warfarin in preparation for the procedure. He is accompanied by his wife, who confirms the time of onset. Evaluation. In the emergency department, blood work is sent for basic chemistries, coagulation profile, and complete blood counts. The patient is en route to the CT scanner. Decision Point A. Based on the above information, what should be the next step in the management of this patient? A1. Examine the patient prior to the CT scan of the brain A2. Obtain more history from his wife A3. Add a CT angiogram to the noncontrast CT of the brain A4. Have the emergency department staff ensure that alteplase is at the bedside A5. Obtain results of the blood work and vital signs The patient undergoes CT of the brain without contrast, which reveals no evidence of an intracranial hemorrhage and no evidence of early ischemic changes. A CT angiogram reveals the presence of a left carotid terminus occlusion. The patient has normal laboratory blood work except for an international normalized ratio (INR) of 1.5. The neurologist speaks with the wife, who reports the patient has no history of surgical procedures. His blood pressure is 190/100 mm Hg. A neurologic examination confirms his NIHSS score of 24, and the patient is now 120 minutes from symptom onset.

Decision Point B. What treatments are warranted at this point? B1. IV alteplase total 0.9 mg/kg with a 10% bolus and the rest over 1 hour B2. IV labetalol 10 mg to lower the blood pressure B3. IV alteplase total 0.6 mg/kg with a 15% bolus and then call interventionist for intraarterial thrombolysis B4. No IV therapy; call interventionist for intraarterial thrombolysis B5. No therapy, as patient has an INR of 1.5 One dose of IV labetalol is administered, and the blood pressure is reduced to 160/80 mm Hg. The glucose level is noted to be 200 mg/dL. The patient weighs 120 kg and is given a bolus of 9 mg of alteplase; an infusion of 81 mg is given over 1 hour. The patient shows no neurologic improvement after 60 minutes and is noted to have an NIHSS score of 24. Decision Point C. What are the options for the next step in the management of this patient? C1. Admit to the neurointensive care unit for further observation C2. Call interventionist and offer patient intraarterial therapy C3. Carefully monitor glucose level C4. Allow blood pressure to rise to help perfusion to the brain The patient is admitted to the neurointensive care unit, and a sliding scale insulin protocol is initiated to help bring the glucose level to below 150 mg/dL. The patient shows little clinical improvement after 24 hours. Decision Point D. What should be the next management step for the patient? D1. Start a heparin drip, given that atrial fibrillation is the cause of the stroke D2. Obtain a CT of the brain to assess for hemorrhagic conversion D3. Obtain an MRI of the brain to assess for extent of injury D4. Consult a neurosurgeon for a hemicraniectomy

WEIGHTS AND COMMENTS

EXPLANATION OF WEIGHTS:
* +5 Unequivocally required for diagnosis or effective treatment, without which management would be negligent * +3 Important for diagnosis and treatment but not immediately necessary * +1 Potentially useful for diagnosis and treatment (routine studies fall into this category) * 0 Neutral impact, neither clearly helpful nor harmful under given circumstances * -1 Not harmful, but nonproductive, time-consuming, and not cost-effective * -3 Nonproductive and potentially harmful * -5 Totally inappropriate and definitely harmful; may threaten life A1. Examine the patient prior to the CT scan of the brain +3 It is important in the setting of an acute ischemic stroke to have a system in place to increase efficiency. If the patient is already en route for a CT scan, this time may be used to obtain more history, clarify the time of onset, and gather pertinent information about surgical history in order to determine if the patient is suitable for IV alteplase. Once the patient has returned, it is important to perform a thorough examination that, along with the NIHSS score, will help to determine the severity of the clinical deficit.

A2. Obtain more history from his wife +3 If the patient's family member is not at the bedside to corroborate the history, it is helpful to attempt to contact witnesses. The emergency medical services (EMS) team generally records contact information for witnesses or next of kin. Sometimes the time of onset can only be determined from the EMS team's discussion with witnesses at the scene. If ambiguity exists about the clinical history, phone calls can help clarify matters. A3. Add a CT angiogram to the noncontrast CT of the brain +1 CT angiography is being increasingly used at institutions to assess for a large artery occlusion at the time of clinical presentation. This test requires placement of an 18-gauge IV into the antecubital vein and may sometimes delay the noncontrast head CT. For a patient within the window for IV alteplase therapy, a noncontrast head CT is the only test required to decide whether the therapy is warranted. A4. Have the emergency department staff ensure that alteplase is at the bedside +5 Many institutions have implemented a "clot box" that is available in the emergency department for patients with acute ischemic stroke. It is helpful to notify the emergency department nurse to have alteplase available at the bedside at the time of examination and while the patient is undergoing a CT scan. Delays can occur if the medication is not available at the bedside when a decision has been made to proceed with treatment. This step ensures efficiency and avoids time delays for administration of alteplase. A5. Obtain results of the blood work and vital signs +5 The results of the blood work are crucial as there are laboratory values that may exclude this patient from treatment with IV alteplase. A glucose level less than 50 mg/dL or greater than 400 mg/dL, a platelet count less than 100,000, or an INR greater than 1.7 are considered relative contraindications for administration of the medication. The blood pressure is important to monitor as blood pressure elevation has been linked to hemorrhagic conversion after alteplase administration. B1. IV alteplase total 0.9 mg/kg with a 10% bolus and the rest over 1 hour -3 The patient has a contraindication to the administration of the medication with an elevated blood pressure of 190/100 mm Hg. Prior to treatment with thrombolysis, the blood pressure should be reduced to less than 185/110 mm Hg. B2. IV labetalol 10 mg to lower the blood pressure +5 Administration of IV antihypertensive medications can be performed prior to treatment with thrombolysis. A total of three doses of IV labetalol can be attempted. If a patient requires a continuous infusion of antihypertensive medication, then treatment with IV thrombolysis is contraindicated. B3. IV alteplase total 0.6 mg/kg with a 15% bolus and then call interventionist for intraarterial thrombolysis 0 This treatment modality is currently being investigated as part of a phase 3 clinical trial in which patients are randomized to treatment with standard IV alteplase (0.9 mg/kg total dose) and compared with patients treated with two-thirds of the dose followed by intraarterial delivery of thrombolytics. The results of this study will aid in answering this important question for patients with large vessel occlusions. B4. No IV therapy; call interventionist for intraarterial thrombolysis 0 Patients with exclusions to IV thrombolysis, such as recent surgery, or elevated INRs can be considered for mechanical or pharmacologic treatment with intraarterial therapy. In the example given, the patient's blood pressure was lowered with one dose of labetalol, and he has no exclusions to IV thrombolysis. The patient should be considered for IV thrombolysis first. B5. No therapy, as patient has an INR of 1.5 -3 An INR level greater than 1.7 is an exclusion for IV alteplase. This patient had an INR of 1.5, which should not exclude him from consideration for therapy. C1. Admit to the neurointensive care unit for further observation +3 Patients who have been treated with IV thrombolytics should be admitted to a unit that allows for careful neurologic assessments along with careful monitoring of blood pressure and glucose. Patients admitted to neurointensive care units are found to have better clinical outcomes when compared to general medical and surgical intensive care units for the diagnosis of ischemic stroke. After administration of thrombolytics, patients should not be placed on anticoagulation therapy for at least 24 hours.

C2. Call the interventionist and offer patient intraarterial therapy +1 Patients who have a persistent large vessel occlusion after administration of IV alteplase may be candidates for rescue therapy with endovascular approaches. It is hoped that the ongoing Interventional Management of Stroke Trial III (IMS III) will address the question of efficacy of combined IV plus intraarterial therapy versus IV therapy alone. Studies have shown that the recanalization rate of thrombus after administration of IV alteplase is dependent on the location of the thrombus. Clots in more proximal locations (ie, carotid terminus) have a lower recanalization rate compared with distal middle cerebral artery branches. On a caseby-case basis, consideration can be given to endovascular therapy for such clinical situations until data from the randomized controlled study become available. C3. Carefully monitor glucose level +3 Recent evidence suggests that hyperglycemia is linked with higher rates of intracranial hemorrhage after administration of thrombolytics. In patients with elevated glucose levels, it may be of benefit to treat and carefully monitor glucose levels, but it is important to avoid hypoglycemia as this may be more detrimental. Ongoing studies are determining whether insulin drip protocols lead to improved outcomes in patients who have suffered an acute ischemic stroke, and they may help to guide how aggressively glucose should be controlled in the acute setting. C4. Allow blood pressure to rise to help perfusion to the brain 0 Studies suggest that in the setting of a large vessel occlusion, induced hypertension may help to reduce clinical deficits by improving perfusion to the tissue. For patients receiving thrombolytics, keeping the blood pressure below 185/110 mm Hg aids in reducing the risk of hemorrhage. For the patient in the clinical scenario presented, aggressively lowering the blood pressure too quickly may be harmful, while targeting a blood pressure above normotensive may be more beneficial. D1. Start a heparin drip, given that atrial fibrillation is the cause of the stroke -3 The patient is now 24 hours from administration of alteplase, but no imaging study has been performed to determine the size of the infarct or whether hemorrhage is present. Hemorrhage, particularly petechial hemorrhage, may be clinically asymptomatic in patients with large strokes. Because there is concern for a large infarct based on the clinical examination, heparin at this time point may place the patient at a high risk for hemorrhagic transformation. Given that the risk of stroke from atrial fibrillation is 6% per year, the day-today risk is relatively low and probably does not justify the risk of hemorrhage that would be associated with the use of heparin at this time. D2. Obtain a CT of the brain to assess for hemorrhagic conversion +3 A CT scan 24 hours after thrombolysis allows the clinician to identify the extent of injury in this instance as well as assess for early signs of edema, particularly given the concern for a large infarct. If hemorrhage is present, it is important to discuss the prognosis as well as the goals of therapy with the family. Patients with large infarcts and global aphasia with right-sided weakness may require a feeding tube for nutrition and will likely suffer significant disability, and the family will need education about caring for the patient. D3. Obtain an MRI of the brain to assess for extent of injury 0 An MRI of the brain can help to define the severity of the brain injury on diffusion-weighted maps early in the stroke course. In the current clinical scenario, a noncontrast CT 24 to 48 hours after admission can often give the same degree of information. Evidence of a large infarct on diffusion-weighted maps on MRI may help the clinician decide which patients are at high risk for malignant cerebral edema and brain herniation from a massive stroke. D4. Consult a neurosurgeon for a hemicraniectomy 0 Given the age of the patient and the fact that the clinical deficit is in the left hemisphere, hemicraniectomy may be a lifesaving measure but will not help to reduce the clinical deficit. Recent studies have shown that younger patients appear to derive the most benefit from such procedures and that older patients are often left with significant disability and full dependence of care. No randomized controlled study has been completed to date to help address this question. Several studies were initiated, but none was completed.